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SARS-CoV-2 positivity rates associated with circulating 25-hydroxyvitamin D levels.

Take Home Message

Vitamin D deficiency and obesity increases risk of testing positive for COVID-19.

Results

  • The COVID-19 positivity rate was higher in the 39,190 patients with “deficient”25(OH)D values (<50 nmol/L) (12.5%) than in the 27,870 patients with “adequate” values (75–85 nmol/L) (8.1%) and the 12,321 patients with values ³137.5 nmol/L (5.9%).
  • The decrease in positivity rate associated with 25(OH)D levels appeared to plateau as values approached 137.5 nmol/L; COVID-19 positivity rates were similar between the 4,016 patients with values 137.5-147.5 nmol/L (6.0%) and the 8,305 patients with higher values (5.9%).
  • COVID-19 positivity rates were significantly higher in the 9,529 patients from predominately black non-Hispanic zip codes (15.7%) and the 26,242 patients from predominately Hispanic zip codes (12.8%) than in the 112,281 patients from predominately white non-Hispanic zip codes (7.2%).
  • Mean 25(OH)D levels were significantly higher in patients from predominately white non-Hispanic zip codes (82.5 ± 29.75 nmol/L) than in patients from predominately black non-Hispanic (72.75 ± 27.5 nmol/L) or Hispanic (72 ± 26.75 nmol/L) zip codes. Regression analysis indicated a strong correlation between 25(OH)D levels and COVID-19 positivity in each of these groups.
  • Compared to the 67,667 patients age ³60 years, the 120,362 younger patients had significantly higher COVID-19 positivity (10.2% vs. 7.7%) and significantly lower mean 25(OH)D levels (73.5 ± 27 nmol/L vs. 88.5 ± 30.25 nmol/L).
  • Compared to the 130,473 female patients, the 61,305 male patients had significantly higher COVID-19 positivity (10.7% vs. 8.7%) and significantly lower mean 25(OH)D levels (78.25 ± 28.5 nmol/L vs. 79.75 ± 29.5 nmol/L).

Who

A total of 191,779 patients (median age = 54 years, range 40.4–64.7 years; 68% women) from all 50 US states with COVID-19 results from tests performed March 9, 2020 through June 19, 2020 and matching 25(OH)D results from the preceding 12 months were included.

Things to Keep in Mind

  • Causality cannot be concluded in the association between vitamin D status and the risk of COVID-19 because of this study’s retrospective design.
  • Limitations of this study include that testing for COVID-19 was based on selection factors, including the presence and gravity of symptoms and exposure to infected individuals.
  • High-risk groups, such as healthcare workers and first responders, were also more likely to be tested.
  • Another limitation is that race/ethnicity estimates were based on aggregate U.S.Census proportions by zip code.
  • There may be many other potentially confounding factors that were neither identified nor controlled for in this study.

Author’s Conclusions

These results demonstrate an inverse relationship between circulating 25(OH)D levels and COVID-19 positivity. For the entire population, those who had a circulating level of 25(OH)D <50 nmol/L had a 54% higher positivity rate compared to those who had a blood level of 75–85 nmol/L. The risk of COVID-19 positivity continued to decline until the serum levels reached 137.5 nmol/L. Northern and central latitudes, predominately Hispanic zip codes, predominately black non-Hispanic zip codes, age <60 years and male sex were independently associated with both 25(OH)D levels and COVID-19 positivity.

Study Design

  • This study is a retrospective, observational analysis of deidentified test results from a clinical laboratory, Quest Diagnostics.
  • A Quest Diagnostics-wide unique patient identifier was used to match all results of COVID-19 testing performed March 9, 2020 through June 19, 2020, with 25(OH)D results from the preceding 12 months.
  • Residential zip code data was also required to match with US Census data and perform analyses of race/ethnicity proportions and latitude. Patient data were linked to estimated race/ethnicity proportions reported by zip code in the 2018 5-year American Community Survey (ACS). Latitude for each zip code, acquired from SAS reference data, was stratified into three groups: >40 degrees (“northern”); 32–40 degrees (“central”); or <32 degrees (“southern”).
  • Total 25(OH)D measurements were categorized as follows: <50 nmol/L was ‘deficient’, 50–72.5 nmol/L was ‘suboptimal’, and ³75 nmol/L was ‘optimal’.
  • Vitamin D seasonality was adjusted for with a model based on a previous 25(OH)D3 study, utilizing Quest Diagnostics results that fit the present study data well.

Reference

Kaufman HW, Niles JK, Kroll MH, Bi C, Holick MF. SARS-CoV-2 positivity rates associated with circulating 25-hydroxyvitamin D levels. PLoS One. 2020 Sep 17;15(9):e0239252. doi: 10.1371/journal.pone.0239252. PMID: 32941512; PMCID: PMC7498100.

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